Abstract：Objective：To investigate the effect of Liangxue Xiaofeng Decoction on Acetyl-Histone H4，histone acetyltransferase 1 （HAT1），acetyltransferase P300，deacetylase sirtuin （SIRT） 3 and SIRT5 in HaCaT cells，and to further discuss the mechanism of acetylation in the pathogenesis change of psoriasis. Methods：The effect of Liangxue Xiaofeng Decoction on the survival rate of HaCaT cells was detected by MTT method， and the following groups of HaCaT were set up： the blank control group， the Liangxue Xiaofeng Decoction group （high-， medium- and lowconcentration Chinese medicine groups），the Tripterygium group and the Curcumin group. The Acetyl-Histone H4 and the protein expressions of HAT1， P300， SIRT3 and SIRT5 were detected by Western Blot before and after administration，and the mRNA expressions of HAT1，P300，SIRT3 and SIRT5 were detected by real-time fluorescent quantitative PCR. Results：According to the results of MTT test，2，1 and 0.25 ng/mL were selected as the dosages of high-，medium- and low-concentration Chinese medicine groups，respectively，2.5 μg /mL in the Tripterygium group and 5 μmol/L in the Curcumin group. When compared with those in the blank control group，the protein expressions of Acetyl-Histone H4， HAT1， P300 and SIRT3 in the Tripterygium group， high- and medium-concentration Chinese medicine groups were increased （P＜0.05）， and the protein expressions of SIRT5 were decreased （P＜0.05）. When compared with those in the blank control group，mRNA expressions of HAT1，P300 and SIRT3 were increased in the Tripterygium group and the high-concentration Chinese medicine group， and the mRNA expressions of SIRT5 were decreased （P＜0.05）. The mRNA expressions of HAT1 and P300 in the medium-concentration Chinese medicine group were increased （P＜0.05）， and the mRNA expression of SIRT5 was decreased （P＜0.05）. The mRNA expression of SIRT5 in the low-concentration Chinese medicine group was decreased （P＜0.05）. The mRNA expression of HAT1 in the Curcumin group was decreased （P＜0.05）. Conclusion： Liangxue Xiaofeng Decoction can up-regulate the expression levels of Acetyl-Histone H4，acetylase HAT1，P300 and deacetylase SIRT3 in HaCaT cells，and downregulate the expression levels of SIRT5. It is speculated that Liangxue Xiaofeng Decoction may treat psoriasis by regulating histone acetylation and related enzymes. Acetylation homeostasis may be an important factor in the pathogenesis change of psoriasis.